Prostate cancer pathology: can we determine which patients can be safely observed?

Educational Objectives

The goal of this program is to improve screening and diagnosis in prostate cancer. After hearing and assimilating this program, the clinician will be better able to:

1. Outline the principles of active surveillance for prostate cancer.

2. Identify patients at low risk for prostate cancer progression.

3. Discuss factors affecting the accuracy of prostate biopsies.

Summary

Active surveillance: goals  —  1) select patients with low risk of progression; 2) monitor patients over time; 3) estab­lish triggers for intervention; 4) consider psychologic burden of cancer diagnosis

Low-risk patients: 1) Gleason score 6 (3+3); 2) clinical stage T1 or T2; 3) prostate-specific antigen (PSA) <10; Lawrentschuk and Klotz (2011) used same criteria as speaker for identifying low-risk patients; other studies used PSA £20 or number of positive cores; >2 positive cores concerning; some studies consider £3 positive cores out of 12 cores still low risk; small amounts of cancer in biopsy do not correlate with amount of cancer in radical prostatectomy (RP); large amounts of cancer in biopsy do correlate with amount of cancer in RP

Algorithm for follow-up: little or no international agreement; based on PSA, Gleason score, clinical stage, age, and comorbidity; also consider <3 cores involved and <50% involvement of any core; variations in core length; 2-cm core with 30% to 40% involvement concerning; follow-up schedule  —  uncertain and variable; consider every 3 mo for 2 yr; perform 10- or 12-core biopsies at 6 mo and 1 yr, then every 3 yr until age 80 yr; ultrasonography of limited value for small tumors

Triggers for intervention: uncertain; consider PSA doubling time of 2 or 3 yr, grade progression, and increase in clinical stage; Cooperberg et al (2011) studied active surveillance in low- and intermediate-risk patients; per­formed ³6 biopsies; outcome variable cancer progression; low-risk patients identified as younger with lower mean PSA and fewer positive cores; no significant differences in Gleason score upgrade at 4-yr follow-up; PSA doubling time slightly higher in low-risk group; active treatment more common in intermediate-risk group; con­cluded that active surveillance can include some patients in intermediate-risk category; no significant difference at RP in biochemical recurrence or nodal status up to 3 yr later; Klotz uses PSA doubling time, biopsies (includ­ing 3-dimensional mapping biopsies), and imaging studies

Biology of cancer: prostate cancer multifocal (average 3.8 cancers/patient); cancer not always palpable or visible; multifocality seen in 33% to 87% of RP specimens; 20% error rate between index cancer and cancer dictating bi­ologic behavior

Studies: 1) Noguchi et al (2003) reported 80% of incidental cancers small and Gleason 6; multifocal tumors not clinically significant in £80% of cases; no effect on preoperative PSA, needle biopsy findings, or recurrence-free survival; no significant predictive value; 2) Cheng et al (2005) identified Gleason 4 (4+3, 4+4, or 4+5) in 16% of nonindex cancers from  RP (cutoff between Gleason 3 and 4 biologically significant); extent of cancer in biopsies and predictive value  —  1) study looked at time to PSA failure after RP in intermediate-risk patients; stratified based on number of positive biopsies; led to 50% cut point for biopsies; 2) study looked at percentage of positive biopsies and PSA failure after RP; stratified into low (<20%), intermediate (20%-54%), and high (³55%) risk; 3) PSA failure after RP with 4-yr follow-up; Gleason score, PSA, and percentage of core positive in biopsy highly predictive of PSA failure; 4) Vollmer and Humphrey (2001) looked at PSA failure in RP; Gleason 5 and percent­age of positive specimens most predictive of survival

Pathology report: World Health Organization and College of American Pathologists recommend including Gleason grade and extent of cancer reported for needle biopsy (with percentage of Gleason 4 and 5 cancer); should also report number of positive cores and measurement of cancer in tissue (in millimeters or percentage of length)

Gleason grading: 1) interobserver variability; 70% agreement on grouping (ie, Gleason <7); problems identifying low grades; cribriform proliferation considered Gleason 7 by some and Gleason 6 or 7 by others; 2) Iczkowski et al (2008) reported RP upgraded Gleason score 7 to 48% from 38% on biopsy; Gleason 6 scores dropped; some argue Gleason 6 (3+3) not worrisome; consider small but significant error rate on biopsies; 3) Gleason pattern 1 and 2 (seen on transurethral resection) may not represent significant malignancy; T1a cancers not routinely treated; Gleason suggested renaming pattern 1 noninvasive epitheliosis, Gleason 2 infiltrating epitheliosis, and Gleason 3 cancer; »50% of Gleason pattern 1 represent atypical adenomatous hyperplasia (architectural mimic of grade 1 cancer); Gleason 5 rarely identified; controversial whether Gleason 6 represents cancer; series of 25,000 RP patients; no deaths in patients with Gleason 6; consider how validity of grading and surgical intervention af­fected outcome

Accuracy of determining risk from biopsy: study (2010) of »550 low-risk patients treated with RP; significant error rate for low-risk patients; 23% upgraded; 5% demonstrated cancer outside prostate (0.9% with seminal vesicle invasion)

Conclusion: undergraded cancer in biopsy vs RP exists in ³10% of cases; higher grades more accurately diagnosed; 25% error rate in staging in contemporary studies; £20% of sampled cancers not determinant of cancer behavior; unknown factors  —1) which men experience unilateral cancer based on preoperative variables; 2) whether prostate cancer dedifferentiates; 3) which variables predict low-risk cancer; 4) impact of improved imaging; active surveil­lance not widely recommended

Readings

Andriole GL et al: Mortality results from a randomized prostate-cancer screening trial. N Engl J Med, 2009 Mar;360(13):1310-9; Bartsch G et al: Prostate cancer mortality after introduction of prostate-specific antigen mass screening in the Federal State of Tyrol, Austria. Urology, 2001 Sep;58(3):417-24; Bartsch G et al: Tyrol Prostate Cancer Demonstration Project: early detection, treatment, outcome, incidence and mortality. BJU Int, 2008 Apr;101(7):809-16; Boyle P, Brawley OW: Prostate cancer: current evidence weighs against population screening. CA Cancer J Clin, 2009 Jul-Aug;59(4):220-4; Cheng L et al: Anatomic distribution and patho­logic characterization of small-volume prostate cancer (<0.5 ml) in whole-mount prostatectomy specimens. Mod Pathol, 2005 Aug;18(8):1022-6; Concato J et al: The effectiveness of screening for prostate cancer: a nested case-control study. Arch Intern Med, 2006 Jan;166(1):38-43; Cooperberg MR et al: Outcomes of active surveillance for men with intermediate-risk prostate cancer. J Clin Oncol, 2011 Jan;29(2):228-34; Crawford ED et al: Comorbidity and mortality results from a randomized prostate cancer screening trial. J Clin Oncol, 2011 Feb;29(4):355-61; Hegarty J et al: Radical prostatectomy versus watchful waiting for prostate cancer. Cochrane Database Syst Rev, 2010 Nov;(11):CD006590; Iczkowski KA et al: Preoperative prediction of unifocal, unilateral, margin-negative, and small volume prostate cancer. Urology, 2008 Jun;71(6):1166-71; Lawrentschuk N, Klotz L: Active surveil­lance for low-risk prostate cancer: an update. Nat Rev Urol, 2011 Apr;8(6):312-20; Lilja H et al: Long-term prediction of prostate cancer up to 25 years before diagnosis of prostate cancer using prostate kallikreins measured at age 44 to 50 years. J Clin Oncol, 2007 Feb;25(4):431-6; Lilja H et al: Prediction of significant prostate cancer diagnosed 20 to 30 years later with a single measure of pros­tate-specific antigen at or before age 50. Cancer, 2011 Mar;117(6):1210-9; Lu-Yao GL, Greenberg ER: Changes in prostate cancer incidence and treatment in USA. Lancet, 1994 Jan;343(8892):251-4; Lu-Yao GL et al: Use of radical prostatectomy among Medi­care beneficiaries before and after the introduction of prostate specific antigen testing. J Urol, 1997 Jun;157(6):2219-22; Noguchi M et al: Prognostic factors for multifocal prostate cancer in radical prostatectomy specimens: lack of significance of secondary cancers. J Urol, 2003 Aug;170(Pt 1):459-63; Quinn M, Babb P: Patterns and trends in prostate cancer incidence, survival, prevalence and mortality. Part I: international comparisons. BJU Int, 2002 Jul;90(2):162-73; Schroder FH et al: Screening and prostate-cancer mor­tality in a randomized European study. N Engl J Med, 2009 Mar;360(13):1320-8; Stamey TA et al: The prostate specific antigen era in the United States is over for prostate cancer: what happened in the last 20 years? J Urol, 2004 Oct;172(4 Pt 1):1297-301; Vollmer RT, Humphrey PA: The relative importance of anatomic and PSA factors to outcomes after radical prostatectomy for prostate can­cer. Am J Clin Pathol, 2001 Dec;116(6):864-70; Welch HG, Albertsen PC: Prostate cancer diagnosis and treatment after the intro­duction of prostate-specific antigen screening: 1986-2005. J Natl Cancer Inst, 2009 Oct;101(19):1325-9.

 

Disclosures

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the plan­ning committee to disclose relevant financial relationships within the past 12 months that might create any personal con­flicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, members of the faculty and planning committee reported nothing to disclose.

Acknowledgements

Dr. Bostwick was recorded at 16th Annual Scottsdale Cancer Symposium, sponsored by Diversified Conference Management, Inc, and held March 3-6, 2011, in Scottsdale, AZ. The Audio-Digest Foundation thanks the speakers and Diversified Conference Management, Inc, for their cooperation in the production of this program. To learn about next year’s Annual Scottsdale Cancer Symposium, go to dcmi.net.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

UR342201

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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